Treatment Of Hepatic Encephalopathy Research Articles

A Systematic Review of the Efficacy and Safety of Fecal Microbiota Transplantation in the Treatment of Hepatic Encephalopathy and Clostridioides difficile Infection in Patients With Cirrhosis.

The microbiome of the human gut and liver coexists by influencing the health and disease state of each system. Fecal microbiota transplantation (FMT) has recently emerged as a potential treatment for conditions associated with cirrhosis, such as hepatic encephalopathy and recurrent/refractory Clostridioides difficile infection (rCDI). We have conducted a systematic review of the safety and efficacy of FMT in treating hepatic encephalopathy and rCDI.A literature search was performed using variations of the keywords “fecal microbiota transplant” and “cirrhosis” on PubMed/MEDLINE from inception to October 3, 2021. The resulting 116 articles were independently reviewed by two authors. Eight qualifying studies were included in the systematic review.A total of 127 cirrhotic patients received FMT. Hepatic encephalopathy was evaluated by cognitive tests, such as the Psychometric Hepatic Encephalopathy Score (PHES) and EncephalApp Stroop test. Not only was there an improvement in the cognitive performance in the FMT cohort, but the improvement was also maintained throughout long-term follow-up. In the treatment of rCDI, the FMT success rate is similar between cirrhotic patients and the general population, although more than one dose may be needed in the former. The rate of serious adverse events and adverse events in the cirrhotic cohort was slightly higher than that in the general population but was low overall.We found evidence that supports the therapeutic potential and safety profile of FMT to treat hepatic encephalopathy and rCDI in cirrhotic patients. Further research will be beneficial to better understand the role of FMT in cirrhosis.

Rifaximin Ameliorates Non-alcoholic Steatohepatitis in Mice Through Regulating gut Microbiome-Related Bile Acids.

Non-alcoholic steatohepatitis (NASH) is the progressive stage of non-alcoholic fatty liver disease (NAFLD). The non-absorbable antibiotic rifaximin has been used for treatment of irritable bowel syndrome, traveling diarrhea, and hepatic encephalopathy, but the efficacy of rifaximin in NASH patients remains controversial. This study investigated the effects and underlying mechanisms of rifaximin treatment in mice with methionine and choline deficient (MCD) diet-induced NASH. We found that rifaximin greatly ameliorated hepatic steatosis, lobular inflammation, and fibrogenesis in MCD-fed mice. Bacterial 16S rRNA sequencing revealed that the gut microbiome was significantly altered in MCD-fed mice. Rifaximin treatment enriched 13 amplicon sequence variants (ASVs) belonging to the groups Muribaculaceae, Parabacteroides, Coriobacteriaceae_UCG-002, uncultured Oscillospiraceae, Dubosiella, Rikenellaceae_RC9_gut_group, Mucispirillum, and uncultured Desulfovibrionaceae. However, rifaximin treatment also reduced seven ASVs in the groups Aerococcus, Oscillospiraceae, uncultured Ruminococcaceae, Bilophila, Muribaculaceae, Helicobacter, and Alistipes in MCD-fed mice. Bile acid-targeted metabolomic analysis indicated that the MCD diet resulted in accumulation of primary bile acids and deoxycholic acid (DCA) in the ileum. Rifaximin delivery reduced DCA levels in MCD-fed mice. Correlation analysis further showed that DCA levels were associated with differentially abundant ASVs modulated by rifaximin. In conclusion, rifaximin may ameliorate NASH by decreasing ileal DCA through alteration of the gut microbiome in MCD-fed mice. Rifaximin treatment may therefore be a promising approach for NASH therapy in humans.

Long Noncoding RNAs Regulate Hyperammonemia-Induced Neuronal Damage in Hepatic Encephalopathy

Background Hyperammonemia can result in various neuropathologies, including sleep disturbance, memory loss, and motor dysfunction in hepatic encephalopathy. Long noncoding RNA (lncRNA) as a group of noncoding RNA longer than 200 nucleotides is emerging as a promising therapeutic target to treat diverse diseases. Although lncRNAs have been linked to the pathogenesis of various diseases, their function in hepatic encephalopathy has not yet been elucidated. Research Design and Methods. To identify the roles of lncRNAs in hepatic encephalopathy brain, we used a bile duct ligation (BDL) mouse model and examined the alteration of neuronal cell death markers and neuronal structure-related proteins in BDL mouse cortex tissue. Furthermore, analysis of the transcriptome of BDL mouse brain cortex tissues revealed several lncRNAs critical to the apoptosis and neuronal structural changes associated with hepatic encephalopathy. Results We confirmed the roles of the lncRNAs, ZFAS1, and GAS5 as strong candidate lncRNAs to regulate neuropathologies in hepatic encephalopathy. Our data revealed the roles of lncRNAs, ZFAS1, and GAS5, on neuronal cell death and neural structure in hyperammonemia in in vivo and in vitro conditions. Conclusion Thus, we suggest that the modulation of these lncRNAs may be beneficial for the treatment of hepatic encephalopathy.

Effects of Low-dose and High-dose Rifaximin in the Treatment of Covert Hepatic Encephalopathy.

Rifaximin is effective in preventing and treating hepatic encephalopathy (HE). This study aimed to investigate the efficacy and safety of different dosages of rifaximin in the treatment of cirrhotic patients with covert HE (CHE). In this single-center, randomized, controlled, open-label study, CHE was diagnosed using a combination of the psychometric HE score and the EncephalApp Stroop test. Cirrhotic patients with CHE were recruited and randomly assigned to low-dose rifaximin 800 mg/day, high-dose rifaximin (1,200 mg/day), and control groups, and were treated for 8 weeks. The sickness impact profile (SIP) scale was used to evaluate the health-related quality of life (HRQOL) of patients. Forty patients were included in the study, 12 were assigned to the low-dose group, 14 to the high-dose group, and 14 patients to the control group. The percentage of patients with CHE reversal was significantly higher in both the low-dose (41.67%, 5/12) and high-dose (57.14%, 8/14) groups than in the control group (7.14%, 1/14) at 8 weeks (p=0.037 and p=0.005, respectively). In addition, both doses of rifaximin resulted in significant improvement of the total SIP score compared with the control group. There were no significant differences in the CHE reversal rate, total SIP score improvement, and incidence of adverse event between the low-dose and high-dose groups (p>0.05). Low-dose rifaximin reverses CHE and improves HRQOL in cirrhotic patients with comparable effects and safety to high-dose rifaximin.

VIII. Diagnosis and Treatment of Hepatic Edema and Hepatic Encephalopathy

VIII. Diagnosis and Treatment of Hepatic Edema and Hepatic Encephalopathy

L-Ornithine L-Aspartate for Prevention and Treatment of Hepatic Encephalopathy in Patients with Cirrhosis

In cirrhosis, the loss of metabolic capacity of periportal and perivenous hepatocytes coupled with the development of portal-systemic shunting frequently results in severe hyperammonemia. Molecular Imaging and Spectroscopic techniques reveal increases in the cerebral metabolic rate for ammonia and increased brain glutamine as a function of the severity of hepatic encephalopathy [HE]. L-Ornithine L-Aspartate [LOLA] is effective for the lowering of blood, muscle and brain ammonia and does so via three independent mechanisms namely [i] the stimulation of ammonia removal via the urea cycle in residual hepatocytes, [ii] prevention of hepatocellular damage due to the production of antioxidants [glutathione, glutamine] and [iii] the prevention of muscle wasting [sarcopenia] thus protecting the ammonia-detoxification pathway via muscle glutamine synthesis. Results of RCTs, systematic reviews and meta-analyses provide evidence for the efficacy of LOLA for the prevention and treatment of HE in all its forms [MHE, OHE, episodic HE, post-TIPSS HE] and for primary, secondary and post-TIPSS prophylaxis. Keywords: L-ornithine L-aspartate; LOLA; Hepatic encephalopathy; Cirrhosis; Treatment; Prevention; Prophylaxis; Ammonia; Hepatoprotection; Sarcopenia; Combination therapy

The importance of electroencephalography in the diagnosis of hepatic encephalopathy due to cirrhosis – a case report

Introduction and aim. Hepatic encephalopathy (HE) associated with cirrhosis of the liver is a neuropsychiatric syndrome, with symptoms ranging from barely detectable changes to deep coma. It frequently occurs in the form of episodes and relapses and can be triggered by external factors. HE severity is graded according to the West Haven criteria. The aim of the study is to draw attention to the ever-important and often key role of electroencephalography in the diagnosis of hepatic encephalopathy, even in today’s era of increasingly advanced diagnostic methods. Description of the case. A 57-year-old patient, professionally active at the time, was admitted to the hospital’s Neurology Department on an emergency basis due to difficulties with standing and moving, orientation disorders and limb tremor. Conclusion. While HE pathogenesis is multifactorial, the most important factors include increased brain exposure to ammonia, intestinal dysbiosis, and endotoxemia inducing a systemic inflammatory response. Patient observation, blood laboratory tests, neuropsychological tests and neurophysiological tests (EEG and evoked potentials) play an important role in establishing the diagnosis. Treatment and secondary prevention of hepatic encephalopathy include elimination of triggers and reduction of ammonia production and improvement of its metabolism.

L-ornithine L-aspartate in acute treatment of severe hepatic encephalopathy: A double-blind randomized controlled trial.

Data on the use of intravenous L-ornithine L-aspartate (LOLA) in the treatment of overt HE (OHE) is limited. We evaluated the role of intravenous LOLA in patients of cirrhosis with OHE grade III-IV. In a double-blind randomized placebo-controlled trial, 140 patients were randomized to a combination of LOLA, lactulose, and rifaximin (n=70) or placebo, lactulose, and rifaximin (n=70). LOLA was given as continuous intravenous infusion at a dose of 30 g over 24 h for 5 days. Ammonia levels, TNF-α, ILs, and endotoxins were measured on days 0 and 5. The primary outcome was the improvement in the grade of HE at day 5. Higher rates of improvement in grade of HE (92.5% vs. 66%, p<0.001), lower time to recovery (2.70 ± 0.46 vs. 3.00 ± 0.87 days, p=0.03), and lower 28-day mortality (16.4% vs. 41.8%, p=0.001) were seen in the LOLA group as compared with placebo. Levels of inflammatory markers were reduced in both groups. Significantly higher reductions in levels of blood ammonia, IL-6, and TNF-α were seen in the LOLA group. Combination of LOLA with lactulose and rifaximin was more effective than only lactulose and rifaximin in improving grades of HE, recovery time from encephalopathy, with lower 28-day mortality.

Saul Brusilow: Understanding and treating diseases of ammonia toxicity

This article reviews the scientific career and accomplishments of the late Dr. Saul Brusilow, Professor of Pediatrics at Johns Hopkins. Dr. Brusilow's career was focused on diseases involving hyperammonemia. He and his colleagues developed a set of drugs that could lower ammonia levels in patients with genetic disorders of the urea cycle by providing alternative pathways for the synthesis of excretable nitrogenous molecules. Those drugs and their derivatives represent one of the earliest and most successful drug therapies for genetic diseases. Turning their attention to brain swelling caused by liver disease, Dr. Brusilow and colleagues developed the Osmotic Gliopathy Hypothesis to help explain the mechanism of ammonia toxicity, postulating that high ammonia drives glutamine synthetase in astrocytes to produce elevated levels of glutamine that act as a potent osmolyte, drawing water into the cell and causing cerebral edema. This hypothesis suggests that inhibiting glutamine synthetase with its well-characterized inhibitor, methionine sulfoximine, might prove therapeutic in cases of hepatic encephalopathy, a conclusion supported by their subsequent studies in animals. But although the drugs developed to treat hyperammonemia resulting from urea cycle disorders were successfully developed and approved by the FDA, the compound suggested as a treatment for hepatic encephalopathy was unable to attract sufficient interest and investment to be tested for use in humans.

Population Pharmacokinetic Analysis to Assist Dose Selection of the L-Ornithine Salt of Phenylacetic Acid.

Background and Objectivel-Ornithine phenylacetate is an intravenous formulation of the l-ornithine salt of phenylacetic acid under development for the treatment of hepatic encephalopathy. Very limited clinical data in patients are available, with a phase II study in target patients not designed for dose finding, to support phase III dose selection in a global development program. The objective of the present population pharmacokinetic modeling and simulation was to evaluate dose selection for target patient populations with a low body weight, ethnicity, and hepatic impairment in a global clinical study.MethodsA population pharmacokinetic model was developed based on plasma concentrations of l-ornithine, phenylacetic acid, and phenylacetylglutamine data from four clinical trials in healthy subjects and patients with stable cirrhosis or hospitalized adult patients with liver cirrhosis and hepatic encephalopathy. A covariate analysis was conducted to identify source of variability to support dose selection for global clinical development of l-ornithine phenylacetate. Phenylacetylglutamine formation in the pharmacokinetic model also quantified pharmacodynamic effects measured by ammonia removal.ResultsBody weight and hepatic function were significant covariates determining phenylacetic acid exposure. After accounting for body weight, there was no difference between tested Caucasian and Asian populations in phenylacetic acid exposure. Renal dysfunction significantly reduced phenylacetylglutamine excretion. However, renal impairment had no impact on plasma phenylacetic acid and free ammonia levels. Exploratory modeling suggested that l-ornithine might enhance the removal of ammonia.ConclusionsWith a flat dosing algorithm, special consideration must be given to patients with a small body size (i.e., body weight ≤ 50 kg) and severe hepatic impairment.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40262-021-01075-1.

Results of using L-ornitin-L-aspartate in the treatment of hepatic encephalopathy in liver transplantation

The aim was to study the results of using various treatment regimens for hepatic encephalopathy for patients with liver cirrhosis before and after liver transplantation and the effect on the incidence and severity of hepatic encephalopathy in the perioperative period, and on the posttransplantation course.Material and methods. Fifty four patients with cirrhosis of various etiologies and the presence of significant hepatic encephalopathy undergoing living donor liver transplantation were included in the study. In the comparison group, patients took lactulose and rifaximin. In the main group, patients took lactulose and rifaximin in combination with L-ornithine-L-aspartate in the preoperative period, and L-ornithine-L-aspartate after liver transplantation for 5 days.Results. The use of L-ornithine-L-aspartate in the complex therapy of hepatic encephalopathy led to significantly reduced time of performing the Number Connection Test, the improvement of cognitive functions in patients by the Montreal Cognitive Assessment, a decreased incidence of stage II–III hepatic encephalopathy and an increased incidence of stage 0-I hepatic encephalopathy in the preoperative period. In the postoperative period, patients of the main group showed a rapid decrease in the severe stages of hepatic encephalopathy (stage II–III) towards less severe forms (stage 0–I) on the 3rd, 5th and 7th days after liver transplantation, and also a faster recovery of cognitive functions, an earlier adequate recovery of consciousness, muscle tone, an earlier possibility of extubation, a shorter length of stay in the intensive care unit, and a decreased postoperative hospital length of stay relatively to the patients of the comparison group.Conclusion. The use of L-ornithine-L-aspartate in the combination therapy for hepatic encephalopathy in the peritransplantation period leads to a significant decrease of the incidence and severity of hepatic encephalopathy, accelerates rehabilitation of patients, reduces postoperative hospital length of stay.

Modern opportunities of pharmacological effect on gut microbiome and motor activity

Currently, lactulose is known to most as a laxative that has a hyperosmotic effect, stimulating intestinal peristalsis. The drug has long established itself as a safe and effective medicine. Lactulose is one of the few drugs that is approved for use in pregnant women and children under 6 months of age with functional constipation. The prebiotic properties of lactulose were discovered in 1957. After research, it was found that it promotes the growth of beneficial bacteria, such as bifidobacteria and lactobacilli. In addition to being used as an effective weak and prebiotic agent, lactulose has been successfully used since 1966 for the treatment of hepatic encephalopathy. The mechanism of action of the drug is that it prevents the absorption of excess ammonia, which is formed in the large intestine, through the hydrolysis of protein and urea by the intestinal microflora. Lactulose, which has a wide range of effects on nitrogen metabolism by the intestinal microflora, affects not only ammonia, but also other bacterial toxins as a result of the studies that have demonstrated the reliable effectiveness of the drug, the world’s leading professional communities have included lactulose in their recommendations as the drug of choice for the treatment of patients with hepatic encephalopathy at any stage of the disease. The article presents current data on the effectiveness and safety of the use of lactulose in various diseases. In addition, attention is paid to such a concept as microbiota. Its functions and influence on the human body are described.

Clinical application and research progress of balloon-occluded retrograde transvenous obliteration in the treatment of gastric varices with decompensated liver cirrhosis

Gastric varices are one of the serious complications of liver cirrhotic portal hypertension. Balloon-occluded retrograde transvenous obliteration (BRTO), as an interventional treatment method, can effectively prevent and control gastroesophagel variceal bleeding. Simultaneously, it has an obvious effect in the treatment of hepatic encephalopathy and liver function improvement. This article reviews the clinical application and research progress of BRTO at home and abroad in recent years, with a view to provide reference for clinical treatment.

Role of circadian rhythm and autonomic nervous system in liver function: a hypothetical basis for improving the management of hepatic encephalopathy.

Hepatic encephalopathy (HE) is a common, incapacitating complication of cirrhosis that affects many patients with cirrhosis. Although several therapies have proven effective in the treatment and prevention of this condition, several patients continue to suffer from covert disease or episodes of relapse. The circadian rhythm has been demonstrated to be pivotal for many body functions, including those of the liver. Here, we explore the impact of circadian rhythm-dependent signaling on the liver and discuss the evidence of its impact on liver pathology and metabolism. We describe the various pathways through which circadian influences are mediated. Finally, we introduce a novel method for improving patient response to drugs aimed at treating HE by utilizing the circadian rhythm. A digital system that introduces a customization-based technique for improving the response to therapies is presented as a hypothetical approach for improving the effectiveness of current medications used for the treatment of recurrent and persistent hepatic encephalopathy.

Low-Dose Lactulose as a Prebiotic for Improved Gut Health and Enhanced Mineral Absorption.

Although medium and high doses of lactulose are used routinely for the treatment of constipation and hepatic encephalopathy, respectively, a wealth of evidence demonstrates that, at low doses, lactulose can also be used as a prebiotic to stimulate the growth of health-promoting bacteria in the gastrointestinal tract. Indeed, multiple preclinical and clinical studies have shown that low doses of lactulose enhance the proliferation of health-promoting gut bacteria (e.g., Bifidobacterium and Lactobacillus spp.) and increase the production of beneficial metabolites [e.g., short-chain fatty acids (SCFAs)], while inhibiting the growth of potentially pathogenic bacteria (e.g., certain clostridia). SCFAs produced upon microbial fermentation of lactulose, the most abundant of which is acetate, are likely to contribute to immune regulation, which is important not only within the gut itself, but also systemically and for bone health. Low-dose lactulose has also been shown to enhance the absorption of minerals such as calcium and magnesium from the gut, an effect which may have important implications for bone health. This review provides an overview of the preclinical and clinical evidence published to date showing that low-dose lactulose stimulates the growth of health-promoting gut bacteria, inhibits the growth of pathogenic bacteria, increases the production of beneficial metabolites, improves mineral absorption, and has good overall tolerability. Implications of these data for the use of lactulose as a prebiotic are also discussed.

Current approach to treatment of minimal hepatic encephalopathy in patients with liver cirrhosis.

Minimal hepatic encephalopathy (MHE) corresponds to the earliest stage of hepatic encephalopathy (HE). MHE does not present clinically detectable neurological-psychiatric abnormalities but is characterized by imperceptible neurocognitive alterations detected during routine clinical examination via neuropsychological or psychometrical tests. MHE may affect daily activities and reduce job performance and quality of life. MHE can increase the risk of accidents and may develop into overt encephalopathy, worsening the prognosis of patients with liver cirrhosis. Despite a lack of consensus on the therapeutic indication, interest in finding novel strategies for prevention or reversion has led to numerous clinical trials; their results are the main objective of this review. Many studies address the treatment of MHE, which is mainly based on the strategies and previous management of overt HE. Current alternatives for the management of MHE include measures to maintain nutritional status while avoiding sarcopenia, and manipulation of intestinal microbiota with non-absorbable disaccharides such as lactulose, antibiotics such as rifaximin, and administration of different probiotics. This review analyzes the results of clinical studies that evaluated the effects of different treatments for MHE.

Retraction

“Efficacy of different drugs in the treatment of minimal hepatic encephalopathy: A network meta‐analysis involving 826 patients based on 10 randomized controlled trials,” by Xiao‐Jun Cai, Lei Wang, and Chun‐Mei Hu, J Cell Biochem. 2018; 8336–8345: The above article, published online on June 22, 2018 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/full/10.1002/jcb.26886), has been retracted by agreement between the journal's Editor in Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC.The retraction has been agreed after the authors found that the experimental methods were flawed and the results are not reliable. The authors collaborated in the investigation initially, but were not available for a final confirmation of the retraction.

Ammonia Removal by Metabolic Scavengers for the Prevention and Treatment of Hepatic Encephalopathy in Cirrhosis.

Effective lowering of circulating ammonia is the mainstay strategy in the prevention and treatment of hepatic encephalopathy in cirrhosis and there is increasing interest in agents with the metabolic potential for the active removal of ammonia by the liver and skeletal muscle by agents including l-ornithine l-aspartate, branched-chain amino acids, as well as the re-purposing of benzoate and phenylacetate currently employed for the control of hyperammonaemia in congenital urea-cycle enzymopathies. Based upon results of multiple systematic reviews with meta-analyses, l-ornithine l-aspartate demonstrably lowers circulating ammonia in patients with cirrhosis with concomitantly improved mental status. Distinct mechanisms responsible include optimisation of hepatic metabolic pathways for ammonia removal as well as direct hepatoprotective effects involving the release of glutathione and of nitric oxide with beneficial effects on hepatic microcirculation. l-ornithine l-aspartate also prevents cirrhosis-related sarcopenia, leading to increased capacity for ammonia removal by skeletal muscle. Branched-chain amino acids continue to be prescribed as nutritional supplements with the potential to result in improvements in liver function. Sodium benzoate, glycerol phenylbutyrate and an analogous compound l-ornithine phenylacetate were also evaluated. Glycerol phenylbutyrate was the only agent with a beneficial effect on both hyperammonaemia and hepatic encephalopathy. None were superior to lactulose for the lowering of blood ammonia.

Efficacy of rifaximin, a poorly absorbed rifamycin antimicrobial agent, for hepatic encephalopathy in Japanese patients.

Rifaximin is recommended as treatment for hepatic encephalopathy (HE) that targets intestinal bacterial flora. Although combined use with synthetic disaccharides is the standard of care worldwide, the therapeutic effects of rifaximin for overt encephalopathy (OHE) in Japanese patients have not been examined sufficiently. We examined the therapeutic effects of rifaximin for OHE in Japanese patients. A total of 76 patients who developed OHE of West Haven gradeII or higher at least once within the 12months before starting rifaximin were included. Blood ammonia levels and the incidence of OHE during the 12months before and after starting rifaximin therapy were compared in a before-and-after study. Rifaximin efficacy and predictors of efficacy were also examined. Post-treatment blood ammonia levels were significantly lower than pretreatment levels. The mean annual number of OHE incidents and intravenous branched-chain amino acid preparations used per patient were significantly lower after starting rifaximin therapy (2.51 vs. 0.76 times/year, p<0.001; and 71.9 vs. 20.7 preparations/year, p=0.003, respectively). The cumulative incidence of hospitalizations associated with HE significantly decreased after rifaximin therapy (hazard ratio 0.187; p<0.001). The efficacy rate, defined as the proportion of patients without OHE during the administration of rifaximin for 1year after starting rifaximin therapy, was 65.8%. Serum albumin ≥2.7g/dl was an independent predictor of efficacy. Rifaximin was associated with decreased blood ammonia levels, lower incidence of OHE, and fewer hospitalizations in Japanese patients with HE. In addition, serum albumin level was an important predictor on efficacy of rifaximin.

Bifidobacterium longum W11: Uniqueness and individual or combined clinical use in association with rifaximin.

Strains belonging to bifidobacteria have been documented as being helpful in adults with intestinal dysbiosis conditions, like those related to irritable bowel syndrome (IBS). This review aims to present the most relevant evidence regarding the efficacy of Bifidobacterium longum W11, a Bifidobacterium used in clinical settings for conditions such as IBS and inflammatory bowel disease. The following electronic databases were systematically searched up to August 2020: MEDLINE (via PubMed), EMBASE, Cochrane Central Database of Controlled Trials (via CENTRAL), Google Scholar, and Clinicaltrials.gov. Data arising from pooled analysis, 7 invitro/pharmacological studies, 7 clinical trials including 1 randomized, double-blind and placebo-controlled, showed that the probiotic strain B.longum W11 has been extensively studied for its efficacy in subjects with IBS with constipation, leading to a significant reduction in symptoms. In particular, its role in alleviating constipation was also confirmed in subjects for whom a low-calorie weight-loss diet led to the slowing down of gut motility. The probiotic characteristics of B. longum W11 were further demonstrated in the treatment of minimal hepatic encephalopathy and hepatic disease. The most remarkable trait of B. longum W11 is its non-transmissible antibiotic resistance, due to a nucleotide polymorphism mutation in the rpoB gene, making it resistant to antibiotics of the rifampicin group, including rifaximin. The co-administration of B. longum W11 and rifaximin in patients with symptomatic uncomplicated diverticular disease brought about a further significant improvement in the clinical condition compared to patients treated with rifaximin alone. B. longum W11 is a probiotic which could synergize with rifaximin as an adjuvant to antibiotic treatment. Taken altogether these findings demonstrate the clinical role of the strain W11 both in some functional and in some inflammatory bowel diseases.